Oncolytic viruses have had a rough decade.
The idea is elegant. Engineer a virus to infect tumor cells, replicate inside them, and trigger an anti-tumor immune response when it kills them. The FDA approved Amgen’s Imlygic for melanoma back in 2015 and everyone thought the floodgates would open.
They didn’t. Imlygic never became a blockbuster. Multiple late-stage oncolytic virus programs have failed in the years since. Just last week, Replimune received a Complete Response Letter from the FDA for RP1 in melanoma, which triggered layoffs and a restructuring.
So when I tell you Akamis Bio reported preliminary data this week from its Phase 1b FORTRESS trial of NG-350A in rectal cancer, your first reaction should probably be skepticism.
Here’s why you should look anyway.
The indication is mismatch repair-proficient locally advanced rectal cancer. pMMR. Also called MSS, microsatellite stable. It’s the hard group. Unlike MSI-high tumors, pMMR rectal cancers don’t respond well to checkpoint inhibitors. Standard of care is chemoradiation, followed by surgery.
A lot of patients end up with permanent colostomies. Clinical complete response rates after chemoradiation alone are roughly 20%.
In the first 10 evaluable FORTRESS patients, NG-350A plus standard chemoradiation produced a 50% composite response rate.
FORTRESS interim: pMMR locally advanced rectal cancer
50%
~20%
Composite response rate in first 10 evaluable patients. CEDAR study with the precursor adenovirus platform showed 41.6% complete response rate vs expected ~20%.
It’s early. Ten patients is not a trial, it’s a data point.
But it’s continuous with what Akamis has been showing with the underlying platform. The CEDAR study with the precursor adenovirus plus chemoradiation got 41.6% complete response rates, compared to the expected ~20% for standard treatment. That’s across more patients.
Here’s what makes Akamis different from most oncolytic virus companies. Their T-SIGn platform does more than kill the tumor with the virus. It uses the virus as a delivery vehicle to turn tumor cells into factories that produce up to five therapeutic proteins simultaneously inside the tumor microenvironment.
NG-350A makes a CD40 agonist antibody. Inside the tumor. Delivered locally at high concentrations without systemic CD40 agonist toxicity, which has killed basically every systemically-delivered CD40 program.
Their second program, NG-641, makes four things at once. A FAP-CD3 bispecific antibody plus CXCL-9, CXCL-10, and interferon alpha. All expressed locally inside tumor tissue.
The Biotech Voyager
Early-stage biotech signals, personalized.
The signals that matter to you. Contextualized and written directly to you. So you cut through the noise and immediately understand why it matters.
That’s a fundamentally different framing than “oncolytic virus.” The virus is the truck. The payload is what matters. Over 200 patients have been treated across Akamis’s programs so far with consistent safety.
The company is private, backed by ARCH, Parker Institute, and Westlake Village BioPartners. They raised $60M in Series A Prime financing in December 2024 linked to a strategic partnership on NG-350A. Operations split between Cambridge, Massachusetts and Oxford, UK.
Look. I’m not going to pretend the oncolytic virus graveyard isn’t full. It is. But most of the companies buried there were trying to do the simple thing: inject a virus, kill tumor cells, hope the immune system cleans up.
Akamis is doing something different. Whether this 50% response rate holds up as FORTRESS enrolls more patients will tell us whether the platform has actual differentiated value, or whether it’s another oncolytic virus story.
pMMR rectal cancer with a 50% response rate would be a meaningful number.
